The objective of the proposed research is to understand the toxicity of ozone at the molecular level. The finding that ozone oxidizes intracellular glutathione in erythrocytes, thereby stimulating activity of glutathione reduction and pentose phosphate pathway metabolism will be examined in other cell types. Oxidation and reduction of glutathione may be general mechanism for cells resistant to ozone. This idea will also be checked using Type II cells of the alveolar epithelium which are resistant to ozone. The erythrocyte will also be used to determine the extent of protein crosslinking caused by ozone especially of membrane proteins. The biosynthesis of lipids in the lung will be studied to see if it is especially inhibited by ozone. This is true in cell-free homogenats, and results will now be extended to tissue slices and intact animals. In the latter case radioactive lipid precursors will be injected into the circulatory system of rats breathing ozone. Subsequent lipid synthesis will be compared in the lung and organs which should be less affected by ozone, e.g., liver and kidney. Studies on reaction of ozone with specific amino acid residues, particularly in membrane proteins, will be continued. The availability for reaction of residues imbedded in the membrane is especially interesting.